title: Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer.
abstract: We evaluated whether genetic variability, as well as menopausal status, modify the association between coffee intake and risk of ovarian cancer. Risk factor information and biologic specimens from three large epidemiological studies, the Nurses' Health Study (NHS), NHSII, and the New England based Case-Control Study of ovarian cancer (NECC) were pooled resulting in 1,354 ovarian cancer cases and 1,851 controls for analysis. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using conditional (NHS/NHSII) and unconditional (NECC) logistic regression. Coffee consumption was not associated with overall risk (OR = 0.99; 95% CI 0.77-1.28); however, there was a suggested increased risk of ovarian cancer among premenopausal women in the NECC only and an inverse association among postmenopausal women. Carrying one or both of the variant CYP19013 A or CYP19027 G alleles was associated with an 18% increased (P for trend = 0.02) and 15% decreased (P for trend = 0.05) risk of ovarian cancer, respectively. Variation in CYP1A1, CYP1A2, or CYP2A6 did not explain the inconsistent reports of coffee intake and risk. Furthermore, we did not observe any clear gene-environment interactions between caffeine metabolizing genes and ovarian cancer. Future studies evaluating mechanisms by which coffee mediates this relationship are warranted.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. nhjok@channing.harvard.edu
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.forename: Allison F
authors.initials: AF
authors.lastname: Vitonis
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
mesh_terms: D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002110:Caffeine / Q000008:administration & dosage* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology* / Q000235:genetics; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
chemical_list: D002110:Caffeine; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065637:Cytochrome P-450 CYP2A6